The effect of iron fortification of complementary foods on infant gut microbiota

辅食中铁强化对婴儿肠道菌群的影响

• 批准号: 8248021
• 负责人: MICHAEL BRUCE ZIMMERMANN
• 金额: $ 41.41万
• 依托单位: SWISS FEDERAL INST OF TECH (ETH ZURICH)
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248021
• 关键词: Area; Bacteremia; Cell Culture Techniques; Child; Communicable Diseases; Country; Dietary Iron; Disease; Dose; Drug Formulations; Enteral; Fermentation; Food; Genotype; Growth; High Pressure Liquid Chromatography; Home environment; In Vitro; Infant; Intervention; Investigation; Iron; Iron deficiency anemia; Knowledge; Malaria; Measures; Metabolic; Metagenomics; Micronutrients; Modeling; Molecular; Powder dose form; Principal Investigator; Production; Research Priority; Safety; Salmonella; Salmonella infections; Sequence Analysis; United States National Institutes of Health; age group; design; fortification; gut microbiota; gut microflora; high risk; in vivo; microbiome; microorganism; pathogen; public health relevance; rRNA Genes; response; working group

DESCRIPTION (provided by applicant): Infants and children < 2 yrs are the age group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron fortification of complementary foods using micronutrient powders is a promising approach. However, WHO has recommended against untargeted use of in-home micronutrient powders that contain the iron RDA for a child in a single dose in malarial areas, until their safety is proven. Research priorities from the U.S. NIH Technical Working Group (2009) "Considerations for the safe and effective use of iron interventions in areas of malaria burden" include: i) effect of iron delivered through different means and formulations on gut microflora; ii) extent to which iron in the gut lumen favors growth of enteric microorganisms with a pathogenic potential. Therefore, we plan to investigate the effect of iron provided in in-home fortification on the infant gut microbiome, using complementary in vitro and in vivo lines of investigation. The focus is on Salmonella spp., as the pathogen most often implicated in studies of bacteremia in severe malaria. The study aims are: i) in vivo, to determine if in-home fortification using an iron-containing micronutrient powder in Kenyan infants at high risk for diarrheal disease and malaria will modify the composition and metabolic activity of the gut microbiota to favor growth of bacterial enteropathogens, and identify the specific enteropathogens that emerge; ii) in vitro, using immobilized infant fecal microflora in a continuous colonic fermentation model inoculated with the specific pathogens identified in the in vivo studies, as well as a cell culture Salmonella infection model, to determine the mechanisms by which colonic iron selects for bacterial enteropathogens, including iron dose, iron form and the molecular and metabolic response of the gut microbiota to iron. To thoroughly characterize the global impact of iron fortification on the gut microbiota and specifically, on enteropathogens, we will apply TTGE, POR, high-throughput 16S rRNA gene sequence analysis, SCFA production by HPLC as well as metagenomic approaches to measure genotype effects. PUBLIC HEALTH RELEVANCE: This project should provide basic knowledge on the interactions between dietary iron and the infant gut microbiota in order to design safe and effective in-home fortification strategies to control iron deficiency anemia in infants in tropical countries with high burdens of infectious disease.

描述（由申请人提供）：婴儿和 2 岁以下儿童是缺铁性贫血发病率最高的年龄组。为这个年龄段的人提供足够的膳食铁是一项挑战，而使用微量营养素粉在家庭补充食品中强化铁是一种有前途的方法。然而，世卫组织建议不要在疟疾地区无针对性地为儿童使用含有每日推荐摄入量铁的家庭微量营养素粉，直到其安全性得到证实。美国国立卫生研究院技术工作组（2009）“在疟疾负担领域安全有效地使用铁干预措施的考虑”的研究重点包括：i）通过不同方式和配方提供的铁对肠道微生物群的影响； ii) 肠腔中的铁有利于具有致病潜力的肠道微生物生长的程度。因此，我们计划利用互补的体外和体内研究线来研究家庭强化中提供的铁对婴儿肠道微生物组的影响。重点是沙门氏菌，它是严重疟疾菌血症研究中最常涉及的病原体。该研究的目的是：i) 在体内，确定对患有腹泻病和疟疾高风险的肯尼亚婴儿使用含铁微量营养素粉进行家庭强化是否会改变肠道微生物群的组成和代谢活动，以有利于细菌性肠道病原体的生长，并确定具体的 出现肠道病原体； ii) 在体外，在连续结肠发酵模型中使用固定的婴儿粪便微生物群，接种体内研究中确定的特定病原体，以及细胞培养沙门氏菌感染模型，以确定结肠铁选择细菌性肠道病原体的机制，包括铁剂量、铁形式以及肠道微生物群对铁的分子和代谢反应。为了彻底表征铁强化对肠道微生物群，特别是肠道病原体的整体影响，我们将应用 TTGE、POR、高通量 16S rRNA 基因序列分析、HPLC 生产 SCFA 以及宏基因组方法来测量基因型效应。 公共健康相关性：该项目应提供有关膳食铁与婴儿肠道微生物群之间相互作用的基础知识，以便设计安全有效的家庭强化策略来控制传染病高负担热带国家婴儿的缺铁性贫血。

项目成果

Iron status and systemic inflammation, but not gut inflammation, strongly predict gender-specific concentrations of serum hepcidin in infants in rural Kenya.

• DOI: 10.1371/journal.pone.0057513
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Jaeggi T;Moretti D;Kvalsvig J;Holding PA;Tjalsma H;Kortman GA;Joosten I;Mwangi A;Zimmermann MB
• 通讯作者: Zimmermann MB

Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites.

连续的体外结肠发酵中铁的低可用性会诱导儿童肠道微生物联盟的强大营养不良，而主代谢产物的降低。

• DOI: 10.1111/j.1574-6941.2012.01461.x
• 发表时间: 2013-01
• 期刊: FEMS microbiology ecology
• 影响因子: 4.2
• 作者: Dostal A;Fehlbaum S;Chassard C;Zimmermann MB;Lacroix C
• 通讯作者: Lacroix C

Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro.

• DOI: 10.1128/mbio.01453-15
• 发表时间: 2015-11-17
• 期刊: mBio
• 影响因子: 6.4
• 作者: Dostal A;Lacroix C;Bircher L;Pham VT;Follador R;Zimmermann MB;Chassard C
• 通讯作者: Chassard C

Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model.

• DOI: 10.1371/journal.pone.0093549
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Dostal A;Gagnon M;Chassard C;Zimmermann MB;O'Mahony L;Lacroix C
• 通讯作者: Lacroix C